DESCRIPTION(provided by applicant): A limited number of physiological and metabolic pathways have been implicated in aging processes, including oxidative damage and inflammation. Polymorphisms have now been identified in many of the genes relevant to these pathways. We hypothesize that some of these polymorphisms have important impacts on behavioral phenotypes, such as physical and cognitive function in older persons. Available measures of physical and cognitive function have substantially higher heritability than life expectancy, have good measurement characteristics, are predictive of health outcomes, and reflect the full range of functioning, including high functioning in old age. The aim of this proposal is to test the association between 255 candidate SNPs in aging pathways with measured physical and cognitive function, in screening and replication sets from four epidemiologic population studies of aging: the English Longitudinal Study of Ageing, the InChianti study, the Baltimore iLongitudinai Study of Ageing and the MRC Cognitive Function and Ageing study. The study is cost effective in adding value to already funded studies. The proposal builds on a successful approach to identifying low or moderate penetrance polymorphisms in genetic association studies in cancer, and will share established lab facilities with a cancer epidemiology program. Previous gene-association work on aging in human populations has often been underpowered and fragmentary in scope, but this proposal involves a targeted survey of candidates and will have good statistical power to identify true associations and exclude false positives. It also builds in replication of findings in independent populations. The proposed study could therefore make a major contribution to 'gene to behavior' science in aging. [unreadable] [unreadable]